David Bennett Sr., a 57-year-old man who received the world's first transplant of a genetically modified pig heart in January, died on Tuesday at the University of Maryland Medical Center (UMMC)—however doctors say it's unclear whether the man's body rejected the transplanted heart.

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The world's first heart transplant from a genetically modified pig

In January, doctors at UMMC successfully performed the transplant, and according to the hospital, the heart "performed very well for several weeks without any signs of rejection."

The heart had 10 genetic modifications—four genes in the heart were inactivated, including one gene that encodes a molecule leading to an aggressive rejection response from a human immune system, the New York Times reports. Another gene that would have allowed the pig's heart to grow after it was implanted was also inactivated.

In addition, six human genes were added to the genome of the pig's heart, aimed at making the heart more tolerable to the human immune system, the Times reports.

According to Bartley Griffith, UMMC's cardiac transplant program director who performed the operation, the pig heart "creates the pulse, it creates the pressure, it is his heart."

However, after several weeks of the heart performing well, Bennett's condition began to deteriorate, according to hospital officials, and he died on Tuesday. A hospital spokesperson said that, at the time of Bennett's death, "there was no obvious cause identified."

Griffith said the hospital's staff is "devastated" by Bennett's death. "He proved to be a brave and noble patient who fought all the way to the end," Griffith said. "Mr. Bennett became known by millions of people around the world for his courage and steadfast will to live."

In a statement, Bennett's son, David Bennett Jr., thanked UMMC for his father's care.

"Their exhaustive efforts and energy, paired with my dad's insatiable will to live, created a hopeful environment during an uphill climb," Bennett Jr. said. "We were able to spend some precious weeks together while he recovered from the transplant surgery, weeks we would not have had without this miraculous effort."

What Bennett's heart transplant means for the future

Bennett's transplant is still considered successful and a major step forward since the pig's heart wasn't immediately rejected and continued to function for over a month, the Times reports.

"As with any first-in-the-world transplant surgery, this one led to valuable insights that will hopefully inform transplant surgeons to improve outcomes and potentially provide lifesaving benefits to future patients," Griffith said.

Muhammad Mohiuddin, a surgeon who pioneered the transplantation process—known as xenotransplantation—at UMMC, said the surgery led to "invaluable insights learning that the genetically modified pig heart can function well within the human body while the immune system is adequately suppressed."

"This was a first step into uncharted territory," said Robert Montgomery, a transplant surgeon at NYU Langone Health. "A tremendous amount of information" will contribute to other transplants in future clinical trials.

"It was an incredible feat that he was kept alive for two months and was able to enjoy his family," Montgomery added.

Karen Maschke from The Hastings Center said patients might look at Bennett's death as a sign that xenotransplantation comes with a short life expectancy, but one person's experience can't predict future experiences. According to Mascke, transplant centers should start educating patients about what they should expect in the future as the science unfolds.

"We hope this story can be the beginning of hope and not the end," Bennett Jr. said. "We also hope that what was learned from [Bennett Sr.'s] surgery will benefit future patients and hopefully one day, end the organ shortage that costs so many lives each year." (Rabin, New York Times, 3/9; Garfinkel, Axios, 3/9; Weintraub, USA Today, 3/10; Neergaard/Johnson, Associated Press, 3/9)